The methyl ester of amphotericin B which has the formula ##STR1## has been prepared by mixing amphotericin B starting material with dimethylsulfoxide and methanol to form a solution of the amphotericin B. The dissolved amphotericin B is then esterified by reaction with diazomethane and the resulting reaction mixture treated with ethyl ether to precipitate the methyl ester.
Belgian Pat. No. 802,512 discloses another procedure for preparing the methyl ester of amphotericin B wherein amphotericin B starting material is mixed with dimethylsulfoxide to form a solution and aqueous ammonia is added to adjust the pH to about 10 (measured on wet indicator paper or after dilution of a sample with water). The solution of amphotericin B is then treated with diazomethane as described above to form the methyl ester.
U.S. Pat. No. 4,035,567 discloses yet another technique for preparing the methyl ester of amphotericin B wherein amphotericin B starting material is mixed with dimethylformamide or hexamethylphosphoric triamide, for a predetermined period; thereafter the above is mixed with sufficient aqueous ammonia to obtain a solution of the amphotericin B, such solution having a pH above 9 in the case where dimethylformamide is used and a pH above 10 in the case where hexamethylphosphoric triamide is used.
After the dissolution of the amphotericin B is effected, esterification is carried out employing diazomethane in accordance with conventional techniques.
While the methyl ester of amphotericin B is particularly valuable for its antifungal properties and in the apparent inability of fungus organisms to develop strains or forms that are resistant to amphotericin B methyl ester, its use has been limited by lack of adequate water solubility.
U.S. Pat. No. 4,041,232 discloses more soluble forms of the methyl ester of amphotericin B which are salts thereof formed by reaction with monocarboxylic amino acids, dicarboxylic amino acids, hydroxy acids, hydrocarbon monocarboxylic acids and hydrocarbon polycarboxylic acids.